Our specific objectives are: (1) To ascertain the fundamental physical nature of the multiple ribonucleases of human blood serum, urine and pancreas; (2) to characterize physical properties of the RNase of leukocytes and the "acid RNase" of urine; (3) to characterize the RNases of normal cerebrospinal fluid and of cerebrospinal fluid showing elevated total RNase activity; (4) to test the hypothesis that the elevated RNase activity observed in the plasma of cancer patients is due, at least in part, to increased concentration of RNase species normally present in plasma; (5) to determine if alterations in the level and/or electrophoretic profile of plasma RNases are correlated with fibrocystic disease of the breast and/or familial history of breast cancer; (6) to compare the level and electrophoretic distribution of plasma RNases before and after resection of malignant tumors and to determine whether the observed differences and/or post-operative level or distribution have prognostic significance; (7) to determine whether analysis of plasma RNase activity may be utilized in the follow-up care of patients; (8) to synthesize the phosphorothiolate analogs of dinucleoside monophosphates and to evaluate their utility as standard substrates for assay of plasma RNase activity. Methods to be employed include standard techniques for purification of enzymes, e.g., column chromatography, and for determination of the physical properties of proteins, e.g., amino acid analysis. Plasma RNase levels of cancer patients will be measured in test tube assays using polymer substrates as well as the novel synthetic substrates. Polyacrylamide gel electrophoresis in conjunction with activity staining for RNase activity will be extensively employed in the fundamental biochemical studies and in the clinical studies.